Design of internal combustion engine systems involves developing control systems for controlling exhaust gas recirculation (EGR) fraction, charge air mass flow (MCF), fueling, injection timing, and so on, to meet performance and emissions targets. Control is often carried out by an engine control module (ECM) (also called the engine control unit (ECU)) or some other controller utilizing an engine map and/or tables in which pre-calibrated reference values are associated with inputs defining a requested operating condition, such as requested engine speed and load. Reference values can include intake or engine out oxygen concentration, engine out “lambda” (λ), which is the ratio of the air/fuel to the stoichiometric air/fuel value, and engine out nitrogen oxides (known as NOx), all of which can be measured directly or indirectly (e.g., by way of a virtual sensor). The ECM/ECU receives the measured or determined actual values as a feedback signal to a controller, which adjusts actuators of the engine system (e.g., actuators controlling an EGR valve, fuel injectors etc.) based on differences between the pre-calibrated reference values and corresponding determined actual values (e.g., NOx or λ sensor feedback signals) to minimize these differences or otherwise cause the measured/determined values to converge towards the pre-calibrated reference values.